Mesotheliomas are hypothesized to develop in response to fibers of critical dimensions. A new model for the induction of mesotheliomas in mice has been developed. Discrete peritoneal nodules develop in response to asbestos, but not to toxic silica particles or nontoxic titanium dioxide particles. Under these conditions, peritoneal macrophages are persistently activated. This model will be used to explore the histogenesis of mesotheliomas and investigate the role of activated macrophages in the development of these tumors. Energy-dispersive x-ray analysis and electron microscopy will be used to determine whether the surface or size of asbestos fibers become modified in vitro. Immunocytochemical typing of intermediate filaments and microspectrofluorimetric assay of DNA content will be used to identify possible precursor lesions of mesotheliomas. Finally, the role of activated macrophages in stimulating proliferation of possible precursor populations and mesotheliomas will be evaluated.